How does the brain store information about emotional experiences? Fear conditioning, a behavioral procedure through which meaningless stimuli are transformed into fear-arousing stimuli, is a valuable tool for studying the neural basis of emotional memory. It is well established that memories, including emotional memories, are formed and stored through plastic changes in synaptic transmission, and considerable evidence points to the amygdala, and specifically its lateral nucleus (LA), as a key site of the plasticity underlying fear conditioning. Past work funded by this grant has implicated excitatory amino acids and downstream intracellular signals (including second messenger pathways and macromolecular synthesis) in the acquisition and storage of conditioned fear memories. In the current proposal we begin to explore the contribution of neuromodulators to synaptic plasticity in LA in relation to fear conditioning. Modulators are important to study because they regulate synaptic transmission and because they recruit mechanisms that allow temporary changes in synaptic plasticity to persist, and thus for stabilizing long-term memory. We focus on the modulator norepinephrine in this proposal because of the mismatch between its long-standing role in the expression and treatment of clinical fear in humans and the relative lack of information about its role in fear conditioning, one of the leading behavioral models for studying fear mechanisms in the brain. Preliminary evidence shows that norepinephrine plays a far greater role in fear conditioning than previously thought. The detailed information about the neural basis of fear conditioning thus offers a neurobiological foundation upon which to further study the role of neuromodulation in fear, and in the development of new approaches for treating pathological fear.